Following treatment of rats with phenelzine (a monoamine oxidase inhibitor, endogenous levels of norepinephrine and 5-hydroxytryptamine in the brain show an initial increase, however there is an adaptive response and amine values return towards control values over 21 days treatment (I.C. Campbell, unpublished results). This study was undertaken to determine whether there was a compensatory decrease in tryptophan hydroxylase or tyrosine hydroxylase which would explain the corresponding drop in amine levels. Preliminary results showed that tyrosine hydroxylase activity in the various brain regions studied was unchanged by phenelzine treatment. Tryptophan hydroxylase activity showed a slight but significant increase in several brain regions. In no region studied was there a decrease in tryptophan hydroxylase activity. We are currently investigating this phenomenon further by examining 1) the kinetics of the reaction (i.e., the effect of phenelzine treatment on the Km of the enzyme for either tryptophan or cofactor), 2) possible activation of the enzyme, 3) corticosterone levels following phenelzine treatment, to see if tryptophan hydroxylase synthesis could be indirectly induced, and 4) tryptophan levels in the brain following phenelzine treatment.